Aging-US

BUFFALO, NY — May 20, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 17, 2025, titled “Dietary associations with reduced epigenetic age: a secondary data analysis of the methylation diet and lifestyle study.” In this study, researchers led by first author Jamie L. Villanueva from the University of Washington and the National University of Natural Medicine, along with corresponding author Ryan Bradley from the National University of Natural Medicine and University of California, investigated how diet influences epigenetic aging. They found that certain plant-based foods containing natural compounds called methyl adaptogens were associated with a decrease in epigenetic age. This effect was measured using DNA methylation, a marker that reflects how the body ages at the cellular level. The findings suggest that targeted food choices may help slow the aging process. Epigenetic age refers to how old a person’s cells appear biologically, rather than their actual age in years. DNA methylation patterns, which are chemical tags on DNA, can indicate whether someone is aging faster or slower than expected. For this study, researchers used Horvath’s epigenetic clock, a widely accepted tool, to measure changes in epigenetic age. The analysis included healthy men aged 50 to 72 who had previously completed an eight-week program featuring a plant-based, nutrient-rich diet, along with guidance on exercise, sleep, and stress management. Researchers focused on individual dietary differences to understand why some participants experienced greater improvements in epigenetic age than others. The study found that those who ate higher amounts of methyl adaptogen foods—including turmeric, rosemary, garlic, berries, green tea, and oolong tea—experienced greater reductions in epigenetic age. These benefits remained significant even after accounting for weight changes and participants’ starting epigenetic age, suggesting that the foods themselves had a direct impact on aging markers. “In hierarchical linear regression, foods investigated as polyphenolic modulators of DNA methylation (green tea, oolong tea, turmeric, rosemary, garlic, berries) categorized in the original study as methyl adaptogens showed significant linear associations with epigenetic age change (B = -1.21, CI = [-2.80, -0.08]), after controlling for baseline epigenetic age acceleration and weight changes.” The natural compounds in methyl adaptogen foods are known to influence how genes behave by affecting DNA methylation. Previous studies have shown that these compounds may support healthy aging and help lower the risk of conditions such as heart disease and cognitive decline. While this study involved a relatively small group of middle-aged men, it adds knowledge to growing global research showing that diets rich in polyphenols—found in vegetables, fruits, and teas—are associated with slower aging. These findings support earlier results from studies on Mediterranean and traditional Japanese diets, both known for their health benefits. Future research should include larger and more diverse populations and use updated epigenetic aging tools to confirm these results. Based on current evidence, this study highlights a practical, food-based strategy that may help reduce epigenetic aging and support long-term health. DOI - https://doi.org/10.18632/aging.206240 Corresponding author - Ryan Bradley - rbradley@nunm.edu To learn more about the journal, connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

In this #episode of the Longevity & Aging Series, Dr. Shubhankar Suman from the Department of Oncology at Georgetown University Medical Center joins host Dr. Evgeniy Galimov to discuss a #research paper he co-authored in Volume 17, Issue 1 of Aging (Aging-US), titled: “Senolytic agent ABT-263 mitigates low- and high-LET radiation-induced gastrointestinal cancer development in Apc1638N/+ mice.” DOI - https://doi.org/10.18632/aging.206183 Corresponding author - Shubhankar Suman - ss2286@georgetown.edu Author interview - https://www.youtube.com/watch?v=ClLO0ERwC0M Video short - https://www.youtube.com/watch?v=M_WEht4vy4w Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206183 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence-associated secretory phenotype, senolytic agent, carcinogenesis, inflammation, β-catenin To learn more about Aging (Aging-US), please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — May 14, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 10, 2025, titled “Impact of Factor Xa inhibitors on cardiovascular events in older patients with nonvalvular atrial fibrillation.” In this study, first author Masahiko Takahashi and corresponding author Keisuke Okawa led a research team from Kagawa Prefectural Central Hospital and Hyogo Medical University that investigated whether Factor Xa inhibitors (Xa-Is)—a type of blood thinner—can reduce the risk of heart-related complications in patients over 80 with nonvalvular atrial fibrillation (NVAF). The study found that patients using Xa-Is experienced significantly fewer cardiovascular problems than those on other anticoagulants. This finding is especially relevant, as older adults face a high risk of both stroke and heart disease. Atrial fibrillation is a common heart rhythm disorder, particularly in the elderly, that increases the risk of blood clots, heart failure, and stroke. Anticoagulants are often prescribed to prevent clots, but not all types have the same effects on heart health. This study focused on comparing Xa-Is—specifically rivaroxaban, apixaban, and edoxaban—with commonly used drugs such as warfarin and dabigatran. Researchers followed more than 1,000 patients aged 80 and above for up to five years to assess the long-term impact of these medications on cardiovascular outcomes. Patients who used Xa-Is had significantly lower rates of heart failure, artery disease, and cardiovascular death. The risk of cardiovascular problems in the Xa-I group was less than half that of those on non-Xa-I medications. These benefits remained even after adjusting for factors like age, existing heart conditions, and kidney function. Additionally, stroke and all-cause death rates were notably lower in the Xa-I group. “Xa-Is may be useful for not only anticoagulation but also the prevention of cardiovascular events in very old patients with NVAF.” What makes Xa-Is different, according to the researchers, is their ability to inhibit a specific biological pathway—known as Factor Xa–PAR2—that contributes to inflammation, fibrosis, and damage in blood vessels and heart tissue. This effect extends beyond their traditional role in preventing blood clots. Although the study was conducted at a single medical center in Japan, its rigorous design and long follow-up period enhance the reliability of the findings for real-world clinical decision-making. While further studies, especially across multiple centers, are needed to confirm the full range of benefits, this study strongly suggests that Xa-Is may offer broader cardiovascular protection for very old patients. The findings could influence how clinicians choose blood thinners for elderly individuals with atrial fibrillation, potentially improving both survival and quality of life in this growing population. DOI - https://doi.org/10.18632/aging.206238 Corresponding author - Keisuke Okawa - k-ookawa@chp-kagawa.jp Video short - https://www.youtube.com/watch?v=YtbYpfVDVDI Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206238 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Factor Xa inhibitor, atrial fibrillation, older patient, cardiovascular events To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Werner syndrome is a rare condition marked by accelerated aging. A recent study, featured as the cover paper in Aging (Aging-US), Volume 17, Issue 4, led by researchers at the University of Oslo and international collaborators, suggests that nicotinamide adenine dinucleotide (NAD+), a vital molecule involved in cellular energy production, may be key to understanding this disease and developing future strategies to manage it. Understanding Werner Syndrome Werner syndrome (WS) is a rare genetic condition that causes people to age more quickly than normal. By their 20s or 30s, individuals with WS often show signs typically associated with older age, such as cataracts, hair loss, thinning skin, and heart disease. This premature aging is caused by mutations in the WRN gene, which normally helps repair DNA and protect cells from damage. While the WRN gene’s role in maintaining genetic stability is well understood, the reasons behind the rapid decline of cells in WS patients are still not fully clear. The Study: Investigating NAD+ in Werner Syndrome Nicotinamide adenine dinucleotide levels naturally decline with age. In the study titled “Decreased mitochondrial NAD+ in WRN deficient cells links to dysfunctional proliferation,” researchers investigated whether this decline is more severe in people with WS and whether restoring NAD+ levels could help slow the aging process in these patients. Full blog - https://aging-us.org/2025/05/fighting-premature-aging-how-nad-could-help-treat-werner-syndrome/ Paper DOI - https://doi.org/10.18632/aging.206236 Corresponding author - Evandro F. Fang - e.f.fang@medisin.uio.no Video short - https://www.youtube.com/watch?v=WpRpi8TYPfU Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206236 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Werner syndrome, premature aging, NAD+, mitochondria, proliferation To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — May 13, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 7, 2025, titled “Pharmacological recapitulation of the lean phenotype induced by the lifespan-extending sulfur amino acid-restricted diet.” In this study, the research team, led by first author Naidu B. Ommi and corresponding author Sailendra N. Nichenametla from the Orentreich Foundation for the Advancement of Science Inc., investigated whether the drug buthionine sulfoximine (BSO) could replicate the effects of sulfur amino acid restriction (SAAR), a challenging diet known to reduce obesity. The study found that BSO produced similar reductions in fat mass and weight gain. This drug-based approach may offer a simpler and safer treatment for obesity, especially for those unable to follow strict dietary plans. Obesity and metabolic disorders raise the risk of chronic illnesses like heart disease, diabetes, and Alzheimer’s disease. While SAAR, a diet low in the amino-acids methionine and cysteine, has shown powerful health benefits in animal studies, its translation to humans has been limited by adherence challenges. This new study explored whether BSO, a compound that lowers glutathione (GSH) levels in the body, could mimic SAAR’s effects without dietary restriction. Researchers tested four groups of obese mice on high-fat diets. One group received the SAAR diet, another was given a regular diet plus BSO, while two control groups received either no treatment or a supplement that increased GSH levels. The BSO-treated mice showed lower fat mass, reduced liver fat, and prevented weight gain, results comparable to those on the SAAR diet. These benefits occurred without reducing food intake or muscle mass, making BSO a particularly promising treatment option. “BSO mice exhibited all SAAR-induced changes, with two notable differences, i.e., a smaller effect size than that of the SAAR diet and a higher predilection for molecular changes in kidneys than in the liver.” Additional findings revealed that both the SAAR diet and BSO influenced metabolic activity by activating pathways related to fat storage, but they did so in different organs. The SAAR diet had stronger effects in the liver, while BSO acted more in the kidneys. Both interventions increased levels of the amino acid serine, which is associated with lower fat production. Unlike many obesity treatments that suppress appetite or reduce muscle, BSO helped prevent fat accumulation while preserving lean mass and food consumption. No signs of liver or kidney toxicity were observed during the 13-week study, suggesting the drug’s safety at the tested dose. Since BSO has previously been evaluated in human clinical trials for other conditions, repurposing it for metabolic diseases may be relatively straightforward. However, the researchers point out that there should be further studies in both animals and humans. If successful, this strategy could provide a practical alternative to difficult-to-maintain diets and help more people manage weight long-term. DOI: https://doi.org/10.18632/aging.206237 Corresponding author: Sailendra N. Nichenametla – snichenametla@orentreich.org Video short - https://www.youtube.com/watch?v=AcCzYTIElGY Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords: aging, buthionine sulfoximine, thiols, serine, anti-obesity drugs To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — May 7, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 4, 2025, titled “Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.” A research team led by first author Mauricio Moel and corresponding author Stefanie L. Morgan from AgelessRx conducted a clinical trial to determine whether low-dose, intermittent rapamycin could safely improve healthspan in older adults. The findings suggest rapamycin may offer measurable benefits for physical function and overall well-being, reinforcing its potential as a safe intervention to support healthy aging. Aging remains the leading cause of chronic conditions such as heart disease, diabetes, and dementia. While medical advances have extended lifespan, many people still experience declining health and reduced mobility in later years. This growing gap between lifespan and healthspan has driven interest in therapies that target aging itself. Rapamycin, an FDA-approved drug originally used in transplant medicine, has drawn attention for its ability to influence aging-related pathways in animal studies. Until recently, its safety and benefits in healthy human populations were largely unknown. The PEARL trial is the longest study so far to explore rapamycin’s use for longevity in healthy aging adults. Researchers followed 114 participants aged 50 to 85 over 48 weeks in a randomized, double-blind, placebo-controlled design. Participants received either a placebo or 5 mg or 10 mg of compounded rapamycin once per week. The study’s primary goal was to measure changes in visceral fat, while secondary outcomes included lean muscle mass, blood markers, and quality-of-life assessments. The trial found that low-dose rapamycin was safe and well-tolerated, with serious side effects reported at similar rates across all groups. The most frequent minor issue among rapamycin users was mild gastrointestinal discomfort. While no significant reductions in visceral fat were observed, women taking 10 mg of rapamycin showed significant gains in lean muscle and reported reduced pain. In addition, participants taking 5 mg weekly reported improvements in emotional well-being and general health, as measured by validated surveys. “Our findings provide evidence that these rapamycin regimens are well tolerated with minimal adverse effects when administered for at least one year within normative aging individuals.” Researchers noted some limitations, including the relatively small and health-conscious participant group, which may have limited the ability to detect larger effects. The compounded form of rapamycin used also had lower absorption than commercial versions, possibly reducing its impact. Overall, the PEARL trial provides early clinical evidence that low-dose rapamycin may help support physical and emotional well-being in older adults. Further studies with larger and more diverse populations will be essential to confirm the study results and refine dosing strategies for broader application. DOI: https://doi.org/10.18632/aging.206235 Corresponding author: Stefanie L. Morgan – stefanie@agelessrx.com Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords: rapamycin, aging, healthspan, longevity, geroscience To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — May 6, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 2, 2025, titled “Fisetin ameliorates vascular smooth muscle cell calcification via DUSP1-dependent p38 MAPK inhibition.” In this study, researchers at Johannes Kepler University Linz found that fisetin, a natural substance found in fruits and vegetables, helps protect blood vessels from hardening, which is a common problem in older adults and people with kidney disease. This discovery highlights fisetin’s potential to prevent vascular calcification and reduce cardiovascular damage caused by aging and chronic kidney disease. The research, led by first author Mehdi Razazian and corresponding author Ioana Alesutan, focused on vascular calcification—a condition in which blood vessels stiffen due to calcium deposits. This process is common in aging and chronic kidney disease and increases the risk of heart attacks and strokes. Using human and mouse study models, the researchers tested fisetin’s ability to prevent this calcification in vascular smooth muscle cells (VSMC), which play a key role in maintaining vessel health. Fisetin, known for its anti-inflammatory and antioxidant properties, significantly reduced calcium buildup and calcification markers under stress conditions that mimic disease. The team also discovered that fisetin suppresses activity in a signaling pathway called p38 MAPK, which is known to promote calcification. This effect depends on a protein called DUSP1. When DUSP1 was blocked, fisetin could no longer protect the cells, showing that this protein is essential for its anti-calcification activity. The researchers confirmed fisetin’s protective effects in isolated mouse arteries and in living mice treated with high doses of vitamin D, which typically increases arterial calcification. “Mechanistically, fisetin requires the phosphatase DUSP1 to inhibit p38 MAPK in order to mediate its protective effect on VSMC calcification.” Importantly, the researchers tested fisetin under conditions similar to human disease. When VSMCs were exposed to blood serum from kidney dialysis patients—a condition known to trigger vascular calcification—fisetin again reduced calcium buildup and protected the cells. These findings suggest fisetin could be useful in countering the harmful vascular effects seen in chronic kidney disease. This study adds to growing evidence that fisetin may protect blood vessels from aging-related damage. While more research is needed before it can be used in clinical treatments, the study highlights fisetin as a promising candidate for slowing or preventing vascular calcification. The findings could have broad implications for aging populations and individuals with kidney disease, who are at greater risk for heart problems due to vascular stiffening. Read the full paper: DOI: https://doi.org/10.18632/aging.206233 Corresponding author: Ioana Alesutan – ioana.alesutan@jku.at Keywords: aging, vascular calcification, vascular smooth muscle cells, fisetin, dual-specificity phosphatase 1, p38 MAPK ______ To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY – May 5, 2025 – Aging (Aging-US), #published by Impact Journals, is pleased to #announce its participation at the upcoming Society for Scholarly Publishing (SSP) 47th Annual Meeting. The #event will take place from May 28-30, 2025, in Baltimore, Maryland. Attendees are invited to visit Booth No. 209 to meet members of the Aging (Aging-US) team. The 2025 meeting theme, “Reimagining the Future of Scholarly Publishing at the Intersection of Value and Values,” underscores the urgency of adapting to rapid technological change, including AI, and addressing growing concerns around research integrity and trust. These priorities align closely with our mission to foster open, reliable, and impactful scientific communication in the field of aging and age-related diseases. In addition, the Longevity & Aging Series - hosted by Dr. Evgeniy Galimov and presented by Aging (Aging-US) - is a Finalist for a Society for Scholarly Publishing (SSP) 2025 EPIC Award in the Video/Film category. Winners will be announced at the EPIC Awards Celebration on May 29. We look forward to connecting with SSP 2025 attendees to share more about Aging (Aging-US) and our publishing initiatives. To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Aging (Aging-US) invites #submissions for a Special Collection dedicated to the theme of cellular #senescence, spanning its basic mechanisms, physiological and pathological functions, and clinical applications. This collection is published in memory of Professor Judith Campisi, a pioneering force in the field of cellular senescence whose groundbreaking work shaped the understanding of senescence in aging, cancer, and tissue homeostasis. Her legacy continues to inspire generations of scientists working to decode the complex biology of senescent cells and their impact on health and disease. We welcome original research articles, reviews, and perspectives on topics including: -Fundamental mechanisms of senescence induction and maintenance -Regulation and context-specific roles of the senescence-associated secretory phenotype (SASP) -Beneficial and detrimental effects of senescent cells in vivo -Senescence in development, aging, regeneration, and age-related diseases -Biomarkers, imaging, and tools for senescence detection and quantification -Therapeutic targeting of senescent cells: senolytics, senomorphics, and clinical translation This Special Collection is guest edited by Han Li and Irina Conboy, both internationally recognized leaders in the study of senescence and aging. Submission Details: -Submission Deadline: January 15, 2026 -Manuscript Format: Please follow the journal’s submission guidelines -Peer Review: All submissions will undergo a rigorous peer-review process -Submission Link: https://aging.msubmit.net/cgi-bin/main.plex

BUFFALO, NY — May 1, 2025 — A new #research paper was #published in Aging (Aging-US) on April 2, 2025, as the #cover of Volume 17, Issue 4, titled “Decreased mitochondrial NAD+ in WRN deficient cells links to dysfunctional proliferation.” In this study, the team led by first author Sofie Lautrup and corresponding author Evandro F. Fang, from the University of Oslo and Akershus University Hospital in Norway, discovered that cells from people with Werner syndrome (WS)—a rare genetic disorder that causes premature aging—have low levels of a molecule called NAD+ in their mitochondria. This molecule is essential for energy production, cellular metabolism, and maintaining cell health. The researchers also found a potential way to improve cell function in WS patients, pointing to new directions for treating age-related decline and other premature aging disorders. Werner syndrome leads to signs of aging much earlier than normal, including problems such as cataracts, hair loss, and atherosclerosis by age 20 to 30. The team found that when the WRN gene is missing or damaged, cells cannot maintain healthy NAD+ levels in their mitochondria. As a result, the cells age more quickly and stop growing properly. When the researchers boosted NAD+ levels using nicotinamide riboside (a vitamin B3 compound) the affected stem cells and skin cells from patients showed less aging and improved mitochondrial activity. “Interestingly, only 24 h treatment with 1 mM nicotinamide riboside (NR), an NAD+ precursor, rescued multiple pathways in the WRN−/− cells, including increased expression of genes driving mitochondrial and metabolism-related pathways, as well as proliferation-related pathways.” The study also found that the WRN gene helps regulate other important genes that control how NAD+ is made in the body. Without WRN, this system becomes unbalanced, which affects how cells function, grow, and respond to stress. Although adding more NAD+ helped some cells look healthier, it could not completely fix the growth problems in other types of lab-grown cells. This suggests that while NAD+ supplementation is beneficial, it cannot fully replace the essential functions of the WRN gene. These findings offer new insights into the biological mechanisms of aging and reinforce the therapeutic potential of targeting NAD+ metabolism in age-related and genetic diseases. Future studies will aim to better understand how subcellular NAD+ regulation interacts with mutations like those seen in WS. Finally, this research supports ongoing efforts to develop NAD+-based treatments that could slow cellular aging and improve quality of life for patients with premature aging conditions. DOI - https://doi.org/10.18632/aging.206236 Corresponding author - Evandro F. Fang - e.f.fang@medisin.uio.no Video short - https://www.youtube.com/watch?v=WpRpi8TYPfU Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206236 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Werner syndrome, premature aging, NAD+, mitochondria, proliferation To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM